Donald L Weaver

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (164)1164.31 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: A pathologist's accurate interpretation relies on identifying relevant histopathological features. Little is known about the precise relationship between feature identification and diagnostic decision making. We hypothesized that greater overlap between a pathologist's selected diagnostic region of interest (ROI) and a consensus derived ROI is associated with higher diagnostic accuracy. We developed breast biopsy test cases that included atypical ductal hyperplasia (n=80); ductal carcinoma in situ (n=78); and invasive breast cancer (n=22). Benign cases were excluded due to the absence of specific abnormalities. Three experienced breast pathologists conducted an independent review of the 180 digital whole slide images, established a reference consensus diagnosis and marked one or more diagnostic ROIs for each case. Forty-four participating pathologists independently diagnosed and marked ROIs on the images. Participant diagnoses and ROI were compared with consensus reference diagnoses and ROI. Regression models tested whether percent overlap between participant ROI and consensus reference ROI predicted diagnostic accuracy. Each of the 44 participants interpreted 39-50 cases for a total of 1972 individual diagnoses. Percent ROI overlap with the expert reference ROI was higher in pathologists who self-reported academic affiliation (69 vs 65%, P=0.002). Percent overlap between participants' ROI and consensus reference ROI was then classified into ordinal categories: 0, 1-33, 34-65, 66-99 and 100% overlap. For each incremental change in the ordinal percent ROI overlap, diagnostic agreement increased by 60% (OR 1.6, 95% CI (1.5-1.7), P<0.001) and the association remained significant even after adjustment for other covariates. The magnitude of the association between ROI overlap and diagnostic agreement increased with increasing diagnostic severity. The findings indicate that pathologists are more likely to converge with an expert reference diagnosis when they identify an overlapping diagnostic image region, suggesting that future computer-aided detection systems that highlight potential diagnostic regions could be a helpful tool to improve accuracy and education.Modern Pathology advance online publication, 20 May 2016; doi:10.1038/modpathol.2016.85.
    No preview · Article · May 2016 · Modern Pathology
  • [Show abstract] [Hide abstract] ABSTRACT: Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with the number of TDLUs and acini count/TDLU using zero-inflated Poisson regression with a robust variance estimator and ordinal logistic regression models, respectively. All analyses were stratified by menopausal status and adjusted for potential confounders. Among premenopausal women, comparing the highest vs. the lowest tertiles, levels of unconjugated estradiol (risk ratio (RR) = 1.74, 95 % confidence interval (CI) = 1.06-2.87, p trend = 0.03), 2-hydroxyestrone (RR = 1.74, 95 % CI = 1.01-3.01, p trend = 0.04), and 4-hydroxyestrone (RR = 1.74, 95 % CI = 0.99-3.06, p trend = 0.04) were associated with significantly higher TDLU count. Among postmenopausal women, higher levels of estradiol (RR = 2.09, 95 % CI = 1.01-4.30, p trend = 0.04) and 16α-hydroxyestrone (RR = 2.27, 95 % CI = 1.29-3.99, p trend = 0.02) were significantly associated with higher TDLU count. Among postmenopausal women, higher levels of EMs, specifically conjugated estrone and 2- and 4-pathway catechols, were also associated with higher acini count/TDLU. Our data suggest that higher levels of serum EMs are generally associated with lower levels of TDLU involution.
    No preview · Article · May 2016
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    [Show abstract] [Hide abstract] ABSTRACT: We examined how pathologists' process their perceptions of how their interpretations on diagnoses for breast pathology cases agree with a reference standard. To accomplish this, we created an individualized self-directed continuing medical education program that showed pathologists interpreting breast specimens how their interpretations on a test set compared with a reference diagnosis developed by a consensus panel of experienced breast pathologists. After interpreting a test set of 60 cases, 92 participating pathologists were asked to estimate how their interpretations compared with the standard for benign without atypia, atypia, ductal carcinoma in situ and invasive cancer. We then asked pathologists their thoughts about learning about differences in their perceptions compared with actual agreement. Overall, participants tended to overestimate their agreement with the reference standard, with a mean difference of 5.5% (75.9% actual agreement; 81.4% estimated agreement), especially for atypia and were least likely to overestimate it for invasive breast cancer. Non-academic affiliated pathologists were more likely to more closely estimate their performance relative to academic affiliated pathologists (77.6 vs 48%; P=0.001), whereas participants affiliated with an academic medical center were more likely to underestimate agreement with their diagnoses compared with non-academic affiliated pathologists (40 vs 6%). Before the continuing medical education program, nearly 55% (54.9%) of participants could not estimate whether they would overinterpret the cases or underinterpret them relative to the reference diagnosis. Nearly 80% (79.8%) reported learning new information from this individualized web-based continuing medical education program, and 23.9% of pathologists identified strategies they would change their practice to improve. In conclusion, when evaluating breast pathology specimens, pathologists do a good job of estimating their diagnostic agreement with a reference standard, but for atypia cases, pathologists tend to overestimate diagnostic agreement. Many participants were able to identify ways to improve.Modern Pathology advance online publication, 8 April 2016; doi:10.1038/modpathol.2016.62.
    Full-text · Article · Apr 2016 · Modern Pathology
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Medical decision making may be influenced by contextual factors. We evaluated whether pathologists are influenced by disease severity of recently observed cases. Methods: Pathologists independently interpreted 60 breast biopsy specimens (one slide per case; 240 total cases in the study) in a prospective randomized observational study. Pathologists interpreted the same cases in 2 phases, separated by a washout period of >6 months. Participants were not informed that the cases were identical in each phase, and the sequence was reordered randomly for each pathologist and between phases. A consensus reference diagnosis was established for each case by 3 experienced breast pathologists. Ordered logit models examined the effect the pathologists' diagnoses on the preceding case or the 5 preceding cases had on their diagnosis for the subsequent index case. Results: Among 152 pathologists, 49 provided interpretive data in both phases I and II, 66 from only phase I, and 37 from phase II only. In phase I, pathologists were more likely to indicate a more severe diagnosis than the reference diagnosis when the preceding case was diagnosed as ductal carcinoma in situ (DCIS) or invasive cancer (proportional odds ratio [POR], 1.28; 95% confidence interval [CI], 1.15-1.42). Results were similar when considering the preceding 5 cases and for the pathologists in phase II who interpreted the same cases in a different order compared with phase I (POR, 1.17; 95% CI, 1.05-1.31). Conclusion: Physicians appear to be influenced by the severity of previously interpreted test cases. Understanding types and sources of diagnostic bias may lead to improved assessment of accuracy and better patient care.
    Full-text · Article · Apr 2016 · Medical Decision Making
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    [Show abstract] [Hide abstract] ABSTRACT: Background: The effect of physician diagnostic variability on accuracy at a population level depends on the prevalence of diagnoses. Objective: To estimate how diagnostic variability affects accuracy from the perspective of a U.S. woman aged 50 to 59 years having a breast biopsy. Design: Applied probability using Bayes' theorem. Setting: B-Path (Breast Pathology) Study comparing pathologists' interpretations of a single biopsy slide versus a reference consensus interpretation from 3 experts. Participants: 115 practicing pathologists (6900 total interpretations from 240 distinct cases). Measurements: A single representative slide from each of the 240 cases was used to estimate the proportion of biopsies with a diagnosis that would be verified if the same slide were interpreted by a reference group of 3 expert pathologists. Probabilities of confirmation (predictive values) were estimated using B-Path Study results and prevalence of biopsy diagnoses for women aged 50 to 59 years in the Breast Cancer Surveillance Consortium. Results: Overall, if 1 representative slide were used per case, 92.3% (95% CI, 91.4% to 93.1%) of breast biopsy diagnoses would be verified by reference consensus diagnoses, with 4.6% (CI, 3.9% to 5.3%) overinterpreted and 3.2% (CI, 2.7% to 3.6%) underinterpreted. Verification of invasive breast cancer and benign without atypia diagnoses is highly probable; estimated predictive values were 97.7% (CI, 96.5% to 98.7%) and 97.1% (CI, 96.7% to 97.4%), respectively. Verification is less probable for atypia (53.6% overinterpreted and 8.6% underinterpreted) and ductal carcinoma in situ (DCIS) (18.5% overinterpreted and 11.8% underinterpreted). Limitations: Estimates are based on a testing situation with 1 slide used per case and without access to second opinions. Population-adjusted estimates may differ for women from other age groups, unscreened women, or women in different practice settings. Conclusion: This analysis, based on interpretation of a single breast biopsy slide per case, predicts a low likelihood that a diagnosis of atypia or DCIS would be verified by a reference consensus diagnosis. This diagnostic grey zone should be considered in clinical management decisions in patients with these diagnoses. Primary funding source: National Cancer Institute.
    Full-text · Article · Mar 2016 · Annals of internal medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Digital breast tomosynthesis (DBT) is emerging as the new standard of care for breast cancer screening based on improved cancer detection coupled with reductions in recall compared to screening with digital mammography (DM) alone. However, many prior studies lack follow-up data to assess false negatives examinations. The purpose of this study is to assess if DBT is associated with improved screening outcomes based on follow-up data from tumor registries or pathology. Retrospective analysis of prospective cohort data from three research centers performing DBT screening in the PROSPR consortium from 2011 to 2014 was performed. Recall and biopsy rates were assessed from 198,881 women age 40–74 years undergoing screening (142,883 DM and 55,998 DBT examinations). Cancer, cancer detection, and false negative rates and positive predictive values were assessed on examinations with one year of follow-up. Logistic regression was used to compare DBT to DM adjusting for research center, age, prior breast imaging, and breast density. There was a reduction in recall with DBT compared to DM (8.7 vs. 10.4 %, p < 0.0001), with adjusted OR = 0.68 (95 % CI = 0.65–0.71). DBT demonstrated a statistically significant increase in cancer detection over DM (5.9 vs. 4.4/1000 screened, adjusted OR = 1.45, 95 % CI = 1.12–1.88), an improvement in PPV1 (6.4 % for DBT vs. 4.1 % for DM, adjusted OR = 2.02, 95 % CI = 1.54–2.65), and no significant difference in false negative rates for DBT compared to DM (0.46 vs. 0.60/1000 screened, p = 0.347). Our data support implementation of DBT screening based on increased cancer detection, reduced recall, and no difference in false negative screening examinations.
    Full-text · Article · Mar 2016 · Breast Cancer Research and Treatment
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    Full-text · Article · Jan 2016 · Breast Cancer Research
  • [Show abstract] [Hide abstract] ABSTRACT: Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLUs), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (peri-lesional). Three measures inversely related to TDLU involution (TDLU count/mm2, median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40-65, were related to MD area (quantified with thresholding software) and volume (assessed with a density phantom) by analysis of covariance, stratified by menopausal status and adjusted for confounders. Among premenopausal women, TDLU count was directly associated with percent peri-lesional MD (P-trend=0.03), but not with absolute dense area/volume. Greater TDLU span was associated with elevated percent dense area/volume (P-trend<0.05) and absolute peri-lesional MD (P=0.003). Acini count was directly associated with absolute peri-lesional MD (P=0.02). Greater TDLU involution (all metrics) was associated with increased nondense area/volume (P-trend≤0.04). Among postmenopausal women, TDLU measures were not significantly associated with MD. Among premenopausal women, reduced TDLU involution was associated with higher area and volumetric MD, particularly in peri-lesional parenchyma. Data indicating that TDLU involution and MD are correlated markers of breast cancer risk suggest that associations of MD with breast cancer may partly reflect amounts of at-risk epithelium. If confirmed, these results could suggest a prevention paradigm based on enhancing TDLU involution and monitoring efficacy by assessing MD reduction.
    No preview · Article · Dec 2015 · Cancer Prevention Research
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Primary care providers and health systems have prominent roles in guiding effective cancer screening. Objective: To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests. Design: Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Participants: Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40-75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50-75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21-65 years). Intervention: Breast, colorectal, or cervical cancer screening. Main measures: Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up. Key results: There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7 % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5-10.3 %; colorectal, 3.0-4.8 %; cervical, 6.3-9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2-95.8 %; colorectal, 43.4-52.0 %; cervical, 29.6-61.4 %). Conclusions: Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities.
    Full-text · Article · Dec 2015 · Journal of General Internal Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Objectives: "Assurance behaviors" in medical practice involve providing additional services of marginal or no medical value to avoid adverse outcomes, deter patients from filing malpractice claims, or ensure that legal standards of care were met. The extent to which concerns about medical malpractice influence assurance behaviors of pathologists interpreting breast specimens is unknown. Methods: Breast pathologists (n = 252) enrolled in a nationwide study completed an online survey of attitudes regarding malpractice and perceived alterations in interpretive behavior due to concerns of malpractice. Associations between pathologist characteristics and the impact of malpractice concerns on personal and colleagues' assurance behaviors were determined by χ2 and logistic regression analysis. Results: Most participants reported using one or more assurance behaviors due to concerns about medical malpractice for both their personal (88%) and colleagues' (88%) practices, including ordering additional stains, recommending additional surgical sampling, obtaining second reviews, or choosing the more severe diagnosis for borderline cases. Nervousness over breast pathology was positively associated with assurance behavior and remained statistically significant in a multivariable logistic regression model (odds ratio, 2.5; 95% confidence interval, 1.0-6.1; P =.043). Conclusions: Practicing US breast pathologists report exercising defensive medicine by using assurance behaviors due to malpractice concerns.
    Full-text · Article · Dec 2015 · American Journal of Clinical Pathology
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    [Show abstract] [Hide abstract] ABSTRACT: Background Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis. Methods One hundred and ninety-five women, ages 40–65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses). Results Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42). Conclusions Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.
    Preview · Article · Dec 2015 · BMC Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: Long non-coding RNAs (lncRNAs) are potential biomarkers for breast cancer risk stratification. LncRNA expression has been investigated primarily by RNA sequencing, quantitative reverse transcription PCR or microarray techniques. In this study, six breast cancer-implicated lncRNAs were investigated by chromogenic in situ hybridisation (CISH). Invasive breast carcinoma (IBC), ductal carcinoma in situ (DCIS) and normal adjacent (NA) breast tissues from 52 patients were screened by CISH. Staining was graded by modified Allred scoring. HOTAIR, H19 and KCNQ1OT1 had significantly higher expression levels in IBC and DCIS than NA (p<0.05), and HOTAIR and H19 were expressed more strongly in IBC than in DCIS tissues (p<0.05). HOTAIR and KCNQ101T were expressed in tumour cells; H19 and MEG3 were expressed in stromal microenvironment cells; MALAT1 was expressed in all cells strongly and ZFAS1 was negative or weakly expressed in all specimens. These data corroborate the involvement of three lncRNAs (HOTAIR, H19 and KCNQ1OT1) in breast tumourigenesis and support lncRNA CISH as a potential clinical assay. Importantly, CISH allows identification of the tissue compartment expressing lncRNA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Article · Aug 2015 · Journal of clinical pathology
  • No preview · Article · Aug 2015 · Cancer Research
  • [Show abstract] [Hide abstract] ABSTRACT: Margin status is important in guiding decisions to re-excise following breast-conserving surgery (BCS) for breast cancer. The College of American Pathologists (CAP) developed guidelines to standardize pathology reporting; however, compliance with margin documentation guidelines has been shown to vary. The aim of this retrospective study was to determine whether compliance with CAP guidelines affects re-excision and mastectomy rates. We identified 1423 patients diagnosed with breast cancer between 1998 and 2006 who underwent BCS with negative margins. CAP compliance was categorized as maximal, minimal, or non-compliant. Statistical analyses were performed comparing the frequency of re-excision and mastectomy after initial BCS according to CAP margin reporting guideline compliance. Data were adjusted for provider facility by including a clustering variable within the regression model. Patients with non-compliant margin reporting were 1.7 times more likely to undergo re-excision and/or mastectomy than those with maximally compliant reporting. Level of compliance was most strongly associated with the frequency of mastectomy; non-compliant margin reporting was associated with a 2.5-fold increase in mastectomy rates compared to maximally compliant reporting. The results did not substantially change when the analyses accounted for clustering at the provider facility level. Our findings suggest that compliance with CAP guidelines in pathology reporting may be associated with variation in re-excision and mastectomy rates following BCS. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Jul 2015 · Breast (Edinburgh, Scotland)
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    Joann G Elmore · Margaret S Pepe · Donald L Weaver
    Full-text · Article · Jul 2015 · JAMA The Journal of the American Medical Association
  • [Show abstract] [Hide abstract] ABSTRACT: General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Jun 2015 · Journal of the National Cancer Institute
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    [Show abstract] [Hide abstract] ABSTRACT: A breast pathology diagnosis provides the basis for clinical treatment and management decisions; however, its accuracy is inadequately understood. To quantify the magnitude of diagnostic disagreement among pathologists compared with a consensus panel reference diagnosis and to evaluate associated patient and pathologist characteristics. Study of pathologists who interpret breast biopsies in clinical practices in 8 US states. Participants independently interpreted slides between November 2011 and May 2014 from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 with atypical hyperplasia (atypia), and 72 benign cases without atypia. Participants were blinded to the interpretations of other study pathologists and consensus panel members. Among the 3 consensus panel members, unanimous agreement of their independent diagnoses was 75%, and concordance with the consensus-derived reference diagnoses was 90.3%. The proportions of diagnoses overinterpreted and underinterpreted relative to the consensus-derived reference diagnoses were assessed. Sixty-five percent of invited, responding pathologists were eligible and consented to participate. Of these, 91% (N = 115) completed the study, providing 6900 individual case diagnoses. Compared with the consensus-derived reference diagnosis, the overall concordance rate of diagnostic interpretations of participating pathologists was 75.3% (95% CI, 73.4%-77.0%; 5194 of 6900 interpretations). Among invasive carcinoma cases (663 interpretations), 96% (95% CI, 94%-97%) were concordant, and 4% (95% CI, 3%-6%) were underinterpreted; among DCIS cases (2097 interpretations), 84% (95% CI, 82%-86%) were concordant, 3% (95% CI, 2%-4%) were overinterpreted, and 13% (95% CI, 12%-15%) were underinterpreted; among atypia cases (2070 interpretations), 48% (95% CI, 44%-52%) were concordant, 17% (95% CI, 15%-21%) were overinterpreted, and 35% (95% CI, 31%-39%) were underinterpreted; and among benign cases without atypia (2070 interpretations), 87% (95% CI, 85%-89%) were concordant and 13% (95% CI, 11%-15%) were overinterpreted. Disagreement with the reference diagnosis was statistically significantly higher among biopsies from women with higher (n = 122) vs lower (n = 118) breast density on prior mammograms (overall concordance rate, 73% [95% CI, 71%-75%] for higher vs 77% [95% CI, 75%-80%] for lower, P < .001), and among pathologists who interpreted lower weekly case volumes (P < .001) or worked in smaller practices (P = .034) or nonacademic settings (P = .007). In this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists' interpretations and the expert consensus-derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concordance for DCIS and atypia. Further research is needed to understand the relationship of these findings with patient management.
    Full-text · Article · Mar 2015 · JAMA The Journal of the American Medical Association
  • [Show abstract] [Hide abstract] ABSTRACT: Elevated mammographic density is a breast cancer risk factor, which has a suggestive, but unproven, relationship with increased exposure to sex steroid hormones. We examined associations of serum estrogens and estrogen metabolites with area and novel volume mammographic density measures among 187 women, ages 40–65, undergoing diagnostic breast biopsies at an academic facility in Vermont. Serum parent estrogens, estrone and estradiol, and their 2-, 4-, and 16-hydroxylated metabolites were measured using liquid chromatography-tandem mass spectrometry. Area mammographic density was measured in the breast contralateral to the biopsy using thresholding software; volume mammographic density was quantified using a density phantom. Linear regression was used to estimate associations of estrogens with mammographic densities, adjusted for age and body mass index, and stratified by menopausal status and menstrual cycle phase. Weak, positive associations between estrogens, estrogen metabolites, and mammographic density were observed, primarily among postmenopausal women. Among premenopausal luteal phase women, the 16-pathway metabolite estriol was associated with percent area (p = 0.04) and volume (p = 0.05) mammographic densities and absolute area (p = 0.02) and volume (p = 0.05) densities. Among postmenopausal women, levels of total estrogens, the sum of parent estrogens, and 2-, 4- and 16-hydroxylation pathway metabolites were positively associated with area density measures (percent: p = 0.03, p = 0.04, p = 0.01, p = 0.02, p = 0.07; absolute: p = 0.02, p = 0.02, p = 0.01, p = 0.02, p = 0.03, respectively) but not volume density measures. Our data suggest that serum estrogen profiles are weak determinants of mammographic density and that analysis of different density metrics may provide complementary information about relationships of estrogen exposure to breast tissue composition.
    No preview · Article · Mar 2015
  • Kimberly Allison · Mara Rendi · Donald Weaver · Joann Elmore
    No preview · Conference Paper · Feb 2015
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    [Show abstract] [Hide abstract] ABSTRACT: BACKGROUND Current data on the pathologic diagnoses of breast biopsy after mammography can inform patients, clinicians, and researchers about important population trends.METHODS Breast Cancer Surveillance Consortium data on 4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology specimens. Trends in diagnoses in biopsies by time and risk factors (patient age, breast density, and family history of breast cancer) were examined for screening and diagnostic mammography (performed for a breast symptom or short-interval follow-up).RESULTSOf the total mammograms, 88.5% were screening and 11.5% diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by biopsies. The frequency of biopsies over time was stable after screening mammograms, but increased after diagnostic mammograms. For biopsies obtained after screening, frequencies of invasive carcinoma increased over time for women ages 40-49 and 60-69, Ductal carcinoma in situ (DCIS) increased for those ages 40-69, whereas benign diagnoses decreased for all ages. No trends in pathology diagnoses were found following diagnostic mammograms. Dense breast tissue was associated with high-risk lesions and DCIS relative to nondense breast tissue. Family history of breast cancer was associated with DCIS and invasive cancer.CONCLUSIONS Although the frequency of breast biopsy after screening mammography has not changed over time, the percentages of biopsies with DCIS and invasive cancer diagnoses have increased. Among biopsies following mammography, women with dense breasts or family history of breast cancer were more likely to have high-risk lesions or invasive cancer. These findings are relevant to breast cancer screening and diagnostic practices. Cancer 2015. © 2015 American Cancer Society.
    Full-text · Article · Jan 2015 · Cancer

Publication Stats

12k Citations
1,164.31 Total Impact Points

Institutions

  • 2004-2014
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 2013
    • Stanford University
      Stanford, California, United States
  • 2005
    • University of Vermont Medical Center
      Burlington, Vermont, United States
  • 1999-2004
    • University of Vermont
      • College of Medicine
      Burlington, Vermont, United States
  • 2002
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States